tbuckley/cabot-search huggingface dataset:
Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing
Authors: Fang Chen, Xingyan Wang, Seon-Kyeong Jang, Bryan C. Quach, J. Dylan Weissenkampen, Chachrit Khunsriraksakul, Lina Yang, Renan Sauteraud, Christine M. Albert, Nicholette D. D. Allred, Donna K. Arnett, Allison E. Ashley-Koch, Kathleen C. Barnes, R. Graham Barr, Diane M. Becker, Lawrence F. Bielak, Joshua C. Bis, John Blangero, Meher Preethi Boorgula, Daniel I. Chasman, Sameer Chavan, Yii-Der I. Chen, Lee-Ming Chuang, Adolfo Correa, Joanne E. Curran, Sean P. David, Lisa de las Fuentes, Ranjan Deka, Ravindranath Duggirala, Jessica D. Faul, Melanie E. Garrett, Sina A. Gharib, Xiuqing Guo, Michael E. Hall, Nicola L. Hawley, Jiang He, Brian D. Hobbs, John E. Hokanson, Chao A. Hsiung, Shih-Jen Hwang, Thomas M. Hyde, Marguerite R. Irvin, Andrew E. Jaffe, Eric O. Johnson, Robert Kaplan, Sharon L. R. Kardia, Joel D. Kaufman, Tanika N. Kelly, Joel E. Kleinman, Charles Kooperberg, I-Te Lee, Daniel Levy, Sharon M. Lutz, Ani W. Manichaikul, Lisa W. Martin, Olivia Marx, Stephen T. McGarvey, Ryan L. Minster, Matthew Moll, Karine A. Moussa, Take Naseri, Kari E. North, Elizabeth C. Oelsner, Juan M. Peralta, Patricia A. Peyser, Bruce M. Psaty, Nicholas Rafaels, Laura M. Raffield, Muagututi’a Sefuiva Reupena, Stephen S. Rich, Jerome I. Rotter, David A. Schwartz, Aladdin H. Shadyab, Wayne H-H. Sheu, Mario Sims, Jennifer A. Smith, Xiao Sun, Kent D. Taylor, Marilyn J. Telen, Harold Watson, Daniel E. Weeks, David R. Weir, Lisa R. Yanek, Kendra A. Young, Kristin L. Young, Wei Zhao, Dana B. Hancock, Bibo Jiang, Scott Vrieze, Dajiang J. Liu
Journal: Nature Genetics (2023)

Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with alternative TWAS methods. These hits and subsequent fine mapping using TESLA point to target genes with biological relevance. In silico drug-repurposing analyses highlight several drugs with known efficacy, including dextromethorphan and galantamine, and new drugs such as muscle relaxants that may be repurposed for treating nicotine addiction.
Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein
Authors: Filippo Bianchini, Virginia Crivelli, Morgan E. Abernathy, Concetta Guerra, Martin Palus, Jonathan Muri, Harold Marcotte, Antonio Piralla, Mattia Pedotti, Raoul De Gasparo, Luca Simonelli, Milos Matkovic, Chiara Toscano, Maira Biggiogero, Veronica Calvaruso, Pavel Svoboda, Tomás Cervantes Rincón, Tommaso Fava, Lucie Podešvová, Akanksha A. Shanbhag, Andrea Celoria, Jacopo Sgrignani, Michal Stefanik, Vaclav Hönig, Veronika Pranclova, Tereza Michalcikova, Jan Prochazka, Giuditta Guerrini, Dora Mehn, Annalisa Ciabattini, Hassan Abolhassani, David Jarrossay, Mariagrazia Uguccioni, Donata Medaglini, Qiang Pan-Hammarström, Luigi Calzolai, Daniel Fernandez, Fausto Baldanti, Alessandra Franzetti-Pellanda, Christian Garzoni, Radislav Sedlacek, Daniel Ruzek, Luca Varani, Andrea Cavalli, Christopher O. Barnes, Davide F. Robbiani
Journal: Science Immunology (2023)

Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2' site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization, and, similar to fp.006 and hr2.016, protects mice expressing human angiotensin-converting enzyme 2 against infection when present as a bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae, including SARS-CoV-2 variants.
Associations between trajectories of obesity prevalence in English primary school children and the UK soft drinks industry levy: An interrupted time series analysis of surveillance data
Authors: Nina T. Rogers, Steven Cummins, Hannah Forde, Catrin P. Jones, Oliver Mytton, Harry Rutter, Stephen J. Sharp, Dolly Theis, Martin White, Jean Adams
Journal: PLoS Medicine (2023)

Sugar-sweetened beverages (SSBs) are the primary source of dietary added sugars in children, with high consumption commonly observed in more deprived areas where obesity prevalence is also highest. Associations between SSB consumption and obesity in children have been widely reported. In March 2016, a two-tier soft drinks industry levy (SDIL) on drinks manufacturers to encourage reformulation of SSBs in the United Kingdom was announced and then implemented in April 2018. We examined trajectories in the prevalence of obesity at ages 4 to 5 years and 10 to 11 years, 19 months after the implementation of SDIL, overall and by sex and deprivation.Data were from the National Child Measurement Programme and included annual repeat cross-sectional measurement of over 1 million children in reception (4 to 5 years old) and year 6 (10 to 11 years old) in state-maintained English primary schools. Interrupted time series (ITS) analysis of monthly obesity prevalence data from September 2013 to November 2019 was used to estimate absolute and relative changes in obesity prevalence compared to a counterfactual (adjusted for temporal variations in obesity prevalence) estimated from the trend prior to SDIL announcement. Differences between observed and counterfactual estimates were examined in November 2019 by age (reception or year 6) and additionally by sex and deprivation quintile. In year 6 girls, there was an overall absolute reduction in obesity prevalence (defined as >95th centile on the UK90 growth charts) of 1.6 percentage points (PPs) (95% confidence interval (CI): 1.1, 2.1), with greatest reductions in the two most deprived quintiles (e.g., there was an absolute reduction of 2.4 PP (95% CI: 1.6, 3.2) in prevalence of obesity in the most deprived quintile). In year 6 boys, there was no change in obesity prevalence, except in the least deprived quintile where there was a 1.6-PP (95% CI: 0.7, 2.5) absolute increase. In reception children, relative to the counterfactual, there were no overall changes in obesity prevalence in boys (0.5 PP (95% CI: 1.0, -0.1)) or girls (0.2 PP (95% CI: 0.8, -0.3)). This study is limited by use of index of multiple deprivation of the school attended to assess individual socioeconomic disadvantage. ITS analyses are vulnerable to unidentified cointerventions and time-varying confounding, neither of which we can rule out.Our results suggest that the SDIL was associated with decreased prevalence of obesity in year 6 girls, with the greatest differences in those living in the most deprived areas. Additional strategies beyond SSB taxation will be needed to reduce obesity prevalence overall, and particularly in older boys and younger children.ISRCTN18042742.
Risk factors for serious infections in ANCA-associated vasculitis
Authors: Balazs Odler, Regina Riedl, Philipp Gauckler, Jae Il Shin, Johannes Leierer, Peter A Merkel, William St. Clair, Fernando Fervenza, Duvuru Geetha, Paul Monach, David Jayne, Rona M Smith, Alexander Rosenkranz, Ulrich Specks, John H Stone, Andreas Kronbichler
Journal: Annals of the Rheumatic Diseases (2023)

Severe infections contribute to morbidity and mortality in antineutrophil cytoplasm antibody-associated vasculitis (AAV). This study aimed to identify risk factors associated with severe infections in participants of the Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial.Data on 197 patients recruited into the RAVE trial were analysed. Participants received either rituximab (RTX) or cyclophosphamide (CYC), followed by azathioprine (AZA). Clinical and laboratory data of patients with and without severe infections (≥grade 3, according to the Common Terminology Criteria for Adverse Events version 3.0) were compared. Risk factors for severe infections were investigated using Cox-regression models.Eighteen of 22 (82%) severe infections occurred within 6 months after trial entry, most commonly respiratory tract infections (15/22, 68%). At baseline, lower absolute numbers of CD19+ cells were observed in patients with severe infections either receiving RTX or CYC/AZA at baseline, while CD5+B and CD3+T cells did not differ between groups. In Cox-regression analysis, higher baseline serum immunoglobulin M levels were associated with the risk of severe infections, whereby a higher baseline total CD19+B cell number and prophylaxis against Pneumocystis jirovecii with trimethoprim-sulfamethoxazole (TMP/SMX) with decreased risk of severe infections. Use of TMP/SMX was associated with lower risk of severe infections in both groups, receiving either RTX or CYC/AZA.The use of low-dose TMP/SMX is associated with reduced risk of severe infections in patients with AAV treated with either RTX or CYC/AZA. Reduced B cell subpopulations at start of treatment might be a useful correlate of reduced immunocompetence.
Unmet need in rheumatology: reports from the Advances in Targeted Therapies meeting, 2022
Authors: Kevin L Winthrop, John D Isaacs, Philip J Mease, Dimitrios T Boumpas, Xenofon Baraliakos, Jacques-Eric Gottenberg, Stefan Siebert, Marta Mosca, Neil Basu, Dana Orange, R Lories, Daniel Aletaha, Iain B McInnes, Tom W J Huizinga, Reinhard E Voll, Ellen M Gravallese, Ferry C Breedveld, Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2023)

To detail the unmet clinical and scientific needs in the field of rheumatology. After a 2-year hiatus due to the SARS-CoV-2 pandemic, the 22nd annual international Advances in Targeted Therapies meeting brought together more than 100 leading basic scientists and clinical researchers in rheumatology, immunology, epidemiology, molecular biology and other specialties. Breakout sessions were convened with experts in five rheumatological disease-specific groups including: rheumatoid arthritis (RA), psoriatic arthritis, axial spondyloarthritis, systemic lupus erythematosus and connective tissue diseases (CTDs). In each group, experts were asked to identify and prioritise current unmet needs in clinical and translational research, as well as highlight recent progress in meeting formerly identified unmet needs. Clinical trial design innovation was emphasised across all disease states. Within RA, developing therapies and trials for refractory disease patients remained among the most important identified unmet needs and within lupus and spondyloarthritis the need to account for disease endotypes was highlighted. The RA group also identified the need to better understand the natural history of RA, pre-RA states and the need ultimately for precision medicine. In CTD generally, experts focused on the need to better identify molecular, cellular and clinical signals of early and undifferentiated disease in order to identify novel drug targets. There remains a strong need to develop therapies and therapeutic strategies for those with treatment-refractory disease. Increasingly it is clear that we need to better understand the natural history of these diseases, including their ‘predisease’ states, and identify molecular signatures, including at a tissue level, which can facilitate disease diagnosis and treatment. As these unmet needs in the field of rheumatic diseases have been identified based on consensus of expert clinicians and scientists in the field, this document may serve individual researchers, institutions and industry to help prioritise their scientific activities.
Ozone Reaction Products Associated with Biomarkers of Cardiorespiratory Pathophysiology
Authors: Linchen He, Charles J. Weschler, Yinping Zhang, Feng Li, Michael H. Bergin, Marilyn Black, Junfeng (Jim) Zhang
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Ozone Reaction Products Associated with Biomarkers of Cardiorespiratory Pathophysiology." American Journal of Respiratory and Critical Care Medicine, 207(9), pp. 1243–1246
C1 inhibitor deficiency enhances contact pathway mediated activation of coagulation and venous thrombosis
Authors: Steven Philip Grover, Tomohiro Kawano, Jun Wan, Pansakorn Tanratana, Zsofia Polai, Young Jun Shim, Omri Snir, Sigrid K. Brækkan, Sophia Dhrolia, Rohan Raj Kasthuri, Tem Bendapudi, Keith R McCrae, Alisa S. Wolberg, John-Bjarne Hansen, Henriette Farkas, Nigel Mackman
Journal: Blood (2023)
The arts in public health policy: progress and opportunities
Authors: Rosie Dow, Katey Warran, Pilar Letrondo, Daisy Fancourt
Journal: The Lancet Public Health (2023)

There is a growing body of evidence indicating the arts have a role to play in promoting good health and preventing and managing illness. WHO has called for governments to take an intersectoral approach, both within and across traditional areas of policy, to realise the potential of the arts for public health. To explore what global progress is being made towards this aim, we present examples of arts and health policy development from diverse government areas: health, arts, local governments, and cross government. These examples, which have been selected from a scoping review of 172 relevant global policy documents, indicate that many health and arts policy makers view the relationship between arts engagement and improved health in quite general terms, although some are investing in more targeted applications of the arts to address specific public health issues. The most promising and concrete commitments are happening when health and arts ministries or agencies work together on policy development.
Safety, tolerability, and immunogenicity of the chimpanzee adenovirus type 3-vectored Marburg virus (cAd3-Marburg) vaccine in healthy adults in the USA: a first-in-human, phase 1, open-label, dose-escalation trial
Authors: Melinda J Hamer, Katherine V Houser, Amelia R Hofstetter, Ana M Ortega-Villa, Christine Lee, Anne Preston, Brooke Augustine, Charla Andrews, Galina V Yamshchikov, Somia Hickman, Steven Schech, Jack N Hutter, Paul T Scott, Paige E Waterman, Mihret F Amare, Victoria Kioko, Casey Storme, Kayvon Modjarrad, Melanie D McCauley, Merlin L Robb, Martin R Gaudinski, Ingelise J Gordon, LaSonji A Holman, Alicia T Widge, Larisa Strom, Myra Happe, Josephine H Cox, Sandra Vazquez, Daphne A Stanley, Tamar Murray, Caitlyn N M Dulan, Ruth Hunegnaw, Sandeep R Narpala, Phillip A Swanson, Manjula Basappa, Jagada Thillainathan, Marcelino Padilla, Britta Flach, Sarah O’Connell, Olga Trofymenko, Patricia Morgan, Emily E Coates, Jason G Gall, Adrian B McDermott, Richard A Koup, John R Mascola, Aurélie Ploquin, Nancy J Sullivan, Julie A Ake, Julie E Ledgerwood, Rebecca Lampley, Brenda Larkin, Pamela Costner, Hope Wilson, Mike Read
Journal: The Lancet (2023)
Multilevel interactions between family and neighbourhood socioeconomic indices in childhood and later risks of self-harm and violent criminality in Denmark: a national cohort study
Authors: Linda Ejlskov, Sussie Antonsen, Jesper N Wulff, Esben Agerbo, Oleguer Plana-Ripoll, Clive E Sabel, Chun Chieh Fan, Wesley K Thompson, Pearl L H Mok, Carsten Bøcker Pedersen, Roger T Webb
Journal: The Lancet Public Health (2023)

A socioeconomically disadvantaged childhood has been associated with elevated self-harm and violent criminality risks during adolescence and young adulthood. However, whether these risks are modified by a neighbourhood's socioeconomic profile is unclear. The aim of our study was to compare risks among disadvantaged young people residing in deprived areas versus risks among similarly disadvantaged individuals residing in affluent areas.
Sex workers health: time to act
Authors: None The Lancet Public Health
Journal: The Lancet Public Health (2023)

"I'm having to take on clients I'd rather not see [and] offer riskier/more emotionally draining services", says a sex worker in the UK charity National Ugly Mugs' report, published on Dec 19, 2022, highlighting the experiences of sex workers facing the UK's cost-of-living crisis. The respondents report fewer clients and remaining clients expecting more for less money. This pressure comes on the heels of sex workers' income, health, and safety having been affected by the COVID-19 pandemic. According to the Global Network of Sex Work Project, curfews and restrictions forced sex workers to decide between losing their income and continuing work with an added layer of criminalisation and related violence.
Uptake of invitations to a lung health check offering low-dose CT lung cancer screening among an ethnically and socioeconomically diverse population at risk of lung cancer in the UK (SUMMIT): a prospective, longitudinal cohort study
Authors: Jennifer L Dickson, Helen Hall, Carolyn Horst, Sophie Tisi, Priyam Verghese, Anne-Marie Mullin, Jon Teague, Laura Farrelly, Vicky Bowyer, Kylie Gyertson, Fanta Bojang, Claire Levermore, Tania Anastasiadis, John McCabe, Neal Navani, Arjun Nair, Anand Devaraj, Allan Hackshaw, Samantha L Quaife, Sam M Janes
Journal: The Lancet Public Health (2023)

Lung cancer screening with low-dose CT reduces lung cancer mortality, but screening requires equitable uptake from candidates at high risk of lung cancer across ethnic and socioeconomic groups that are under-represented in clinical studies. We aimed to assess the uptake of invitations to a lung health check offering low-dose CT lung cancer screening in an ethnically and socioeconomically diverse cohort at high risk of lung cancer.
Influenza vaccination and stroke risk: additional factors should be considered
Authors: Wei-Min Chu, Chih-Wei Chen, James Cheng-Chung Wei
Journal: The Lancet Public Health (2023)

We read with great interest the Article by Jessalyn Holodinsky and colleagues, which reports the association of influenza vaccination with a reduced risk of stroke in adults.1 However, we would like to highlight some key concerns.
Impact of dysexecutive syndrome in quality of life in Alzheimer disease: What we know now and where we are headed
Authors: Michelle Zonkowski Ribas, Gabriela Ferreira Paticcié, Felipe Micelli Noleto, Luís Guilherme Ramanzini, Arthur de Oliveira Veras, Renato Dall'Oglio, Luciano Barroso de Albuquerque Filho, Jaiurte Gomes Martins da Silva, Micael Porto Portela Lima, Beatriz Esmeraldo Teixeira, Gabrielle Nunes de Sousa, André Felipe Costa Alves, Lara Maria Fujita Vieira Lima, Camilla Costa Sallem, Tulia Fernanda Meira Garcia, Isadora Mônica Ponte de Oliveira, Raul Sancho de Carvalho Rocha, Mikaio de Sousa Jucá, Sarah Távora Barroso, Júlio César Claudino dos Santos
Journal: Ageing Research Reviews (2023)
The multiple layers of health inequality
Authors: Naja Hulvej Rod
Journal: The Lancet Public Health (2023)

Reducing health inequality is a major public health priority,1 but public health has so far failed to provide the evidence base needed to fully capture and handle this complex challenge. To address this, health science needs to evolve from focusing primarily on individual exposures and single diseases to a system-oriented approach, considering the dynamics between diseases and events at an individual level, and the subsequent group dynamics at a population level.
A novel endoscopic clip for closing a large perforating wound in a patient undergoing endoscopic full-thickness resection
Authors: Qiang Zhang, Zhen Wang
Journal: Endoscopy (2023)

The through-the-scope twin clip (Micro-Tech Co. Ltd., Nanjing, China), also called a dual action tissue clip, was first reported by us [1] [2]. The clip can pass directly through the working channel of the endoscope to close the wound and is convenient and quick to use. To our knowledge, this was the first time that through-the-scope twin clips were used to close a large perforation in a patient with a submucosal tumor.
Commentary
Authors: Ana Craciun, Michael Bourke
Journal: Endoscopy (2023)

The immersion into the submucosal layer with endoscopic submucosal dissection two decades ago led us to a new era of third-space endoscopy and endoscopic full-thickness resection, whereby many lesions, even with full-thickness muscularis propria involvement, can be safely removed endoscopically. Therefore, endoscopic recognition, characterization, and management of iatrogenic full-thickness mural defects is critical to ensure technical success and safety [1] [2]. The focus has now been increasingly shifting towards developing new devices to close progressively larger defects throughout the gastrointestinal tract. These closure tools, including through-the-scope (TTS) clipping, suture-based, or endoscopic vacuum therapy, need to be adapted to the size and location of the defects. In an experimental study [3] and in this video, Zhang et al. showed the efficacy of novel TTS twin clips (TTS-TCs) for closing wounds ≥ 25 mm, when intertwined with traditional TTS clips, functioning as coadjuvants in reducing submucosal dead space and achieving a firm closure effect. In summary, the TTS-TC holds great promise as a definitive mural closure device as it can be used in a deflated lumen, in situations where access is poor, and promptly without the need for endoscope exchange or reinsertion. Further prospective comparative studies are required to establish efficacy, safety, and cost–effectiveness.
Endoscopy E-Videos – recently published
Journal: Endoscopy (2023)

Comment on: Cold-snare endoscopic mucosal resection of large duodenal laterally spreading tumors: is cold the future gold standard?Endoscopy 2022; 54(S 02): E894-E895DOI: 10.1055/a-1841-5607 Comment on: Direct large flow of venous gas into right atrium and ventricle during endoscopic biliary treatmentEndoscopy 2022; 54(S 02): E877-E878DOI: 10.1055/a-1860-1354 Comment on: Underwater endoloop-assisted endoscopic resection for colorectal pedunculated polypsEndoscopy 2022; 54(S 02): E835-E836DOI: 10.1055/a-1824-5056 Comment on: A novel endoscopic technique for closure of two gastro-gastric fistulas in a single session using an endoscopic helix tacking deviceEndoscopy 2022; 54(S 02): E845-E846DOI: 10.1055/a-1838-3306
Proximal serrated polyp detection rate and post-colonoscopy colorectal cancer: the missing link
Authors: Joep E. G. IJspeert
Journal: Endoscopy (2023)

Colorectal cancer (CRC) is among the most prevalent forms of cancer worldwide and is responsible for a substantial proportion of cancer-related deaths [1]. Colonoscopy with polypectomy of all relevant lesions is vital for the prevention of CRC. Unfortunately, up to 8 % of all CRCs occur after colonoscopy, also demonstrating its limitations [2]. The literature shows that the majority of these so-called post-colonoscopy CRCs (PCCRCs) are due to missed or incompletely resected lesions [3]. Therefore, improving colonoscopy quality seems key to decreasing the incidence of PCCRC.